Preclinical sporadic Alzheimer's disease: target for personalized diagnosis and preventive intervention

Abstract The most opportune time for preventive intervention in sporadic Alzheimer's disease (spAD) is early in its preclinical stage (pcAD), when the odds of preventing or minimizing later disabling neurodegeneration are most favorable. The efficacy of promising preventive interventions should be assessed in patients in the earliest discernible phase of pcAD. This will require application of personalized medicine techniques, with use of suitable biomarkers to detect pcAD in individuals believed to be spAD-prone. This review focuses on the genetic biomarker, apolipoprotein E (apoE) ε4, and on certain neuroimaging biomarkers, such as structural MRI (sMRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), and PET-amyloid tracers capable of delineating the extent and distribution of amyloid-beta (Aβ) deposits in the brain, that can be useful in identifying cognitively normal people who are at enhanced risk of developing spAD. Many years before AD symptoms appear, such neuroimaging procedures can disclose signature abnormalities of brain structure, function, and amyloid levels in cognitively normal apoE ε4 allele carriers and/or individuals with a family history of spAD. Although no effective treatment for spAD is yet available, there is evidence that, by taking a proactive personalized-medicine approach, the practicing physician may be able to reduce risk in AD-prone patients by attending to such modifiable AD risk factors as hypertension, obesity, type 2 diabetes, insulin resistance, hypercholesterolemia, sedentary lifestyle, and current cigarette smoking. Young patients who are ε4 positive should be advised to avoid participation in contact sports or other activities that expose them to risk of traumatic brain injury.